Abstract
The effects of intracerebroventricular (i.cv.) administration of calcitonin gene-related (CGRP) on blood pressure and heart rate (HR), and the underlying mechanisms were studied in conscious rats. CGRP (0.1–3.0 nmol i.cv.) increased mean arterial blood pressure (MABP) and HR. CGRP (3.0 nmol i.cv.) also significantly increased both plasma norepinephrine and epinephrine concentrations. Pretreatment with 16.5 nmol i.cv. CGRP(8–37), a specific CGRP receptor antagonist, significantly inhibited the i.cv. CGRP (1.0 nmol)-induced increases in MABP and HR. Phenoxybenzamine inhibited the i.c.v. CGRP-induced increase in MABP, while propranolol suppressed the tachycardiac response to i.cv. CGRP. Chemical sympathectomy by 6-hydroxydopamine inhibited the increases in MABP and HR produced by i.cv CGRP. These results suggest that the central pressor and tachycardiac effects of i.c.v. CGRP are mediated by catecholamine release due to stimulation of sympathetic nervous system activity, possibly via specific CGRP receptors in the central nervous system.
Similar content being viewed by others
References
Amara GS, Jonas V, Rosenfeld MG, Ong ES, Evans RM (1982) Alternative RNA processing in the calcitonin gene expression generates mRNAs encoding different polypeptide products. Nature 298: 240–245
Brain DS, Williams TJ, Tippins JR, Morris HR, MacIntyre I (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313:54–56
Brown RM, Fisher LA, Rivier J, Spiess J, Rivier C, Vale WW (1982a) Corticotropin-releasing factor: effects on the sympathetic nervous system and oxygen consumption. Life Sci 30:207–210
Brown RM, Fisher LA, Spiess J, Rivier C, Rivier J, Vale WW (1982b) Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 111:928–931
Chiba T, Yamaguchi A, Yamatani T, Nakamura A, Morishita T, Inui T, Fukase M, Noda T, Fujita T (1989) Calcitonin gene-related peptide receptor antagonist human CGRP(8–37). Am J Physiol 256: E331-E335
Fenstermacher JD (1972) Ventriculocisternal perfusion as a technique for studying transport and metabolism within the brain. In: Marks N, Rodnight R (eds) Research methods in neurochemistry, vol 1. Plenum Press, New York, pp 165–178
Ferrari AU, Daffonchio A, Franzalli C, Mancia G (1991) Potentiation of the baroreceptor-heart rate reflex by sympathectomy in conscious rats. Hypertension 18:230–235
Fisher AL, Kikkawa DO, Rivier JE, Amara SG, Evans RM, Rosenfeld MG, Vale WW, Brown MR (1983) Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide. Nature 305:534–536
Gibson JS, Polak JM, Bloom SR, Sabate IM, Mulderry PM, Ghatei MA, McGregor JP, Morrison JFB, Kelly JS, Evans RM, Rosenfeld MG (1984) Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J Neurosci 4: 3101–3111
Goltzman D, Mitchell J (1985) Interaction of calcitonin and calcitonin gene-related peptide at receptor sites in target tissues. Science 227:1343–1345
Han S-P, Naes L, Westfall TC (1990) Inhibition of periarterial nerve stimulation-induced vasodilatation of the mesenteric arterial bed by CGRP(8–37) and CGRP receptor desensitization. Biochem Biophys Res Commun 168:786–791
Hoffman BB, Lefkowitz RJ (1990) Catecholamines and sympathomimetic drugs. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics, 8th edn. Pergamon Press, Oxford New York, pp 187–220
Kawasaki H, Takasaki K, Saito A, Goto K (1988) Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat. Nature 335:164–167
Kostrzewa MR, Jacobowitz DM (1974) Pharmacological actions of 6-hydroxydopamine. Pharmacol Rev 26:199–288
Kruk LZ, Pycock CJ (1983) Noradrenaline. In: Kruk LZ, Pycock CJ (eds) Neurotransmitters and drugs. Croom Helm, Beckenham, pp 42–80
Marshall I, Al-kazwini SJ, Roberts PM, Shepperson NB, Adams M, Craig RK (1986) Cardiovascular effects of human and rat CGRP compared in the rat and other species. Eur J Pharmacol 123: 207–216
Nguyen KQ, Sills MA, Jacobowitz DM (1986) Cardiovascular effects produced by microinjection of calcitonin gene-related peptide into the rat central amygdaloid nucleus. Peptides 7:337–339
Ouchi Y, Kim S, Souza AC, Iijima S, Hattori A, Orimo H, Yoshizumi M, Kurihara H, Yazaki Y (1989) Central effect of endothelin on blood pressure in conscious rats. Am J Physiol 256:H1747-H1751
Rodrigo J, Polak JM, Fernandez L, Ghatei MA, Mulderry P, Bloom SR (1985) Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat, and monkey esophagus. Gastroenterology 88:444–451
Rosenfeld GM, Mermod J-J, Amara SG, Swanson LW, Sawchenko PE, Rivier J, Vale WW, Evans RM (1983) Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304:129–135
Tschopp FA, Tobler PH, Fischer JA (1984) Calcitonin gene-related peptide in the human thyroid, pituitary and brain. Mol Cell Endocrinol 36:53–57
Tschopp FA, Henke H, Petermann JB, Tobler PH, Janzer R, Hokfelt T, Lundberg JM, Cuello C, Fischer JA (1985) Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary. Proc Natl Acad Sci USA 82:248–252
Yoshimura M, Komori T, Nakanishi T, Takahashi H (1993) Estimation of sulphoconjugated catecholamine concentrations in plasma by high-performance liquid chromatography. Ann Clin Biochem 30:135–141
Author information
Authors and Affiliations
Additional information
This study was presented, in part, at the 14th Scientific Meeting of the International Society of Hypertension, held in Madrid, Spain in June, 1992
Correspondence to: Y. Ouchi at the above address
Rights and permissions
About this article
Cite this article
Kuo, Tf., Ouchi, Y., Kim, S. et al. The role of activation of the sympathetic nervous system in the central pressor action of calcitonin gene-related peptide in conscious rats. Naunyn-Schmiedeberg’s Arch Pharmacol 349, 394–400 (1994). https://doi.org/10.1007/BF00170886
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF00170886